Drug delivery systems that specifically deliver active agents to the colon have been recognized as having important therapeutic advantages. It is contemplated in the art that a large number of colonic conditions could be treated more effectively with a lower risk of adverse side reactions if the respective active agent were only released locally, i.e. in the colon or the respective part of the colon. Examples of such colonic disorders include Crohn's disease, ulcerative colitis, colorectal cancer, constipation and diarrhea. Further such drug delivery systems are described to be beneficial for patients in cases where delay in absorption is necessary.
WO 2008/059062 A1 for example describes drug delivery systems that can deliver therapeutic and/or diagnostic agents to the colon. These systems include pectin beads crosslinked with zinc or other divalent cations, wherein these beads are then coated with specific polymers, i.e. polyacrylates. These beads are prepared by dropping the pectin solution which contains the dispersed drug into a curing solution containing zinc cations. Similarly, WO 2009/092333 relates to a device for the process of preparing sodium alginate/chitosan slow release capsules. These systems do not contain any lipids or lipophilic drugs embedded in the beads.
Among the active agents known for the treatment of colonic conditions, short chain fatty acids (SOFA) and in particular butyrate and its derivatives have been described in the literature. These methods described in the literature apply different strategies for delivering the respective short chain fatty acids to the colon.
For example EP 2 289 505 describes a nutritional composition which consists of a core of probiotics, a prebiotic support, a butyric acid compound and one or more gastro-resistant coatings. The composition is used in form of tablets to target the probiotics to the colon and the butyric acid compound is contained in the composition to improve the absorption of probiotics in the intestine.
WO 2010/060914 describes the microencapsulation of butyric acid within a lipid matrix using a spray cooling process. The microcapsules are prepared for animal or human consumption and are intended to protect the butyric acid compound from the acidic gastric environment and increase the absorption on the intestinal level. However, the described digestion tests indicate that only a small part of the microencapsulated butyric acid compounds are in fact delivered to the colon. Similar microcapsules are described e.g. in EP 1 354 520 with the same limitation as described above.
Besides the microencapsulation of butyric acid, some documents describe a prodrug-based strategy using butyric acid esters of carbohydrates. For example U.S. Pat. No. 5,840,860 describes a delivery system for short chain fatty acids which consists of a polysaccharide to which short chain fatty acids are bound by means of an ester or amide bond to generate short chain fatty acid prodrugs. The polysaccharides and the amide or ester bonds within the prodrug are described not to be cleaved in the stomach or small intestine but only by microbial enzymes in the colon. The dose of butyric acids which is actually released in the colon can, however, only hardly be defined because the delivery depends amongst others on the activity of the enzymes in the gut.
Thus, there is still a need for advantageous delivery systems being adapted to deliver active agents, in particular lipophilic or water-insoluble active agents, to the colon.